rs9263809

Variant names:

• chr6-31168800-A-G
• rs9263809
• NM_002701.6:c.405+1416T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002701.6(POU5F1):​c.405+1416T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,166 control chromosomes in the GnomAD database, including 1,736 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1736 hom., cov: 32)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 3 publications found

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.405+1416T>C		intron_variant	Intron 1 of 4	ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.405+1416T>C		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000441888.7	c.-183-2753T>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
POU5F1	ENST00000461401.1	n.443+1416T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22141 AN: 152048 Hom.: 1728 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0923

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.161

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22186 AN: 152166 Hom.: 1736 Cov.: 32 AF XY: 0.143 AC XY: 10609 AN XY: 74386

African (AFR) AF: 0.160 AC: 6636 AN: 41524

American (AMR) AF: 0.133 AC: 2027 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 320 AN: 3468

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5178

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4818

European-Finnish (FIN) AF: 0.115 AC: 1218 AN: 10586

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10789 AN: 67988

Other (OTH) AF: 0.159 AC: 336 AN: 2112

Alfa AF: 0.152 Hom.: 219

Bravo AF: 0.147

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9263809; hg19: chr6-31136577;